Liu Jia, Cao Yukun, Zhu Kuikui, Yao Sheng, Yuan Mei, Kong Xiangchuang, Liu Xiaoming, Li Yumin, Cui Yue, Han Xiaoyu, Zhou Xiaoyue, Meng Rui, Shi Heshui
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
Quant Imaging Med Surg. 2022 Oct;12(10):4771-4785. doi: 10.21037/qims-22-41.
Few studies have focused on the subclinical cardiotoxicity of immune checkpoint inhibitors (ICIs) in cancer patients. This study aimed to evaluate the manifestations of subclinical cardiotoxicity of ICI therapy using cardiovascular magnetic resonance (CMR) and to explore whether CMR parameters can help predict cardiotoxicity at the early stage of ICI therapy.
A prospective, longitudinal study was conducted among patients with lung cancer. The patients were planned to undergo serial CMRs before (baseline), 3 weeks after (1st follow-up), and 3 months after (2nd follow-up) the initiation of ICI therapy, respectively. Patients with 3 CMRs were included in the analysis. Serial quantitative measurements based on CMR were compared using one-way repeated measures analysis of variance (RM-ANOVA). On the basis of cancer therapy-related cardiac dysfunction (CTRCD) observed at the second follow-up, patients were categorized into a CTRCD group and a non-CTRCD group. Baseline clinical and CMR parameters and the relative reduction of left ventricular global strain at the second follow-up was compared between the CTRCD group and the non-CTRCD group. Receiver operating characteristic (ROC) analysis was used to identify CTRCD that developed 3 months after ICI therapy.
A total of 36 patients with 3 CMRs (60.7±9.2 years old, 77.8% male) were included in the analysis. Left ventricular-global radial strain (LV-GRS) decreased significantly at the second follow-up (37.9%±8.5% 33.1%±1.0%; P=0.014), but left ventricular ejection fraction (LVEF) did not change significantly (51.5%±6.0% 49.2%±6.5%; P>0.05). A total of 7 patients (19.4%) had developed CTRCD by the second follow-up. Baseline clinical and CMR parameters did not differ between the CTRCD group and the non-CTRCD group (P>0.05 for all). In the CTRCD group, the left ventricular-global circumferential strains (LV-GCSs) showed significant reductions at both the first and second follow-up (P=0.008 and 0.035, respectively), but the LVEF only showed a significant reduction at the second follow-up (P<0.001). The relative reduction of LV-GRS at the second follow-up was significantly higher in the CTRCD group than in the non-CTRCD group (29.8%±25.8% 6.8%±20.4%; P=0.036) and was used to predict CTRCD developed at the 3-month timepoint after ICI therapy [area under the curve (AUC) =0.759; P=0.036].
In the early stage of ICI therapy, assessment of myocardial strain can be used to detect subclinical left ventricular systolic dysfunction in patients with lung cancer earlier than LVEF. The relative reduction of LV-GRS can be used to predict CTRCD 3 months after ICI therapy.
很少有研究关注免疫检查点抑制剂（ICI）在癌症患者中的亚临床心脏毒性。本研究旨在使用心血管磁共振成像（CMR）评估ICI治疗亚临床心脏毒性的表现，并探讨CMR参数是否有助于在ICI治疗早期预测心脏毒性。
对肺癌患者进行一项前瞻性纵向研究。计划让患者在ICI治疗开始前（基线）、治疗后3周（第一次随访）和治疗后3个月（第二次随访）分别接受系列CMR检查。纳入有3次CMR检查结果的患者进行分析。基于CMR的系列定量测量结果采用单向重复测量方差分析（RM-ANOVA）进行比较。根据第二次随访时观察到的癌症治疗相关心脏功能障碍（CTRCD），将患者分为CTRCD组和非CTRCD组。比较CTRCD组和非CTRCD组的基线临床和CMR参数以及第二次随访时左心室整体应变的相对降低情况。采用受试者工作特征（ROC）分析来识别ICI治疗3个月后发生的CTRCD。
共有36例有3次CMR检查结果的患者（60.7±9.2岁，77.8%为男性）纳入分析。第二次随访时左心室整体径向应变（LV-GRS）显著降低（37.9%±8.5%对33.1%±1.0%；P=0.014），但左心室射血分数（LVEF）无显著变化（51.5%±6.0%对49.2%±6.5%；P>0.05）。到第二次随访时，共有7例患者（19.4%）发生了CTRCD。CTRCD组和非CTRCD组的基线临床和CMR参数无差异（所有P>0.05）。在CTRCD组中，第一次和第二次随访时左心室整体圆周应变（LV-GCS）均显著降低（分别为P=0.008和0.035），但LVEF仅在第二次随访时显著降低（P<0.001）。CTRCD组第二次随访时LV-GRS的相对降低显著高于非CTRCD组（29.8%±25.8%对6.8%±20.4%；P=0.036），并用于预测ICI治疗后3个月时发生的CTRCD[曲线下面积（AUC）=0.759；P=0.036]。
在ICI治疗早期，评估心肌应变比LVEF能更早地检测出肺癌患者的亚临床左心室收缩功能障碍。LV-GRS的相对降低可用于预测ICI治疗3个月后的CTRCD。
